The Malaria Therapeutics Response Portal results from efforts to discover new antimalarial targets targeting multiple stages of Plasmodium parasites and acting by novel mechanisms of action. The data result from primary and secondary screens of a diverse collection of 100,000 compounds having three-dimensional topographic features derived from stereochemical and skeletal elements common in natural products but underrepresented in typical screening collections - compounds now accessible using diversity-oriented synthesis (DOS). The compounds result from short, modular syntheses that facilitate chemical optimization and manufacturing and have computed physical properties that facilitate drug discovery. A primary phenotypic screen was used to identify the subset of compounds that kill P. falciparum counter screens were performed to prioritize molecules with novel mechanisms of action and activities at multiple stages of the parasite life cycle, and genetic and biochemical studies to illuminate mechanisms of action. These efforts yielded several series of multiple-stage antimalarial compounds having unique scaffolds and modulating recently described and novel molecular targets, and we hope that the MTRP will facilitate users' efforts to discover many new compounds having these properties.
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